Researchers Shed Light on Anti-inflammatory Effects of Vitamin D Supplements in MS

Researchers Shed Light on Anti-inflammatory Effects of Vitamin D Supplements in MS
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Vitamin D supplements promote a shift toward an anti-inflammatory state in people with multiple sclerosis (MS) through an increase of two key molecules, IL-27 and TGF-beta 1, a study shows.

These findings add another level of regulation to a previous model linking the intake of vitamin D supplements with higher levels of anti-inflammatory molecules and lower levels of pro-inflammatory molecules in MS patients. These vitamin D-induced molecular changes now were found to be driven by an increased production of IL-27 and TGF-beta 1.

While the data support the notion that taking vitamin D supplements may ease inflammation and nerve cell damage in MS patients, further studies evaluating the association between these vitamin D-associated molecular changes and clinical parameters in MS patients are needed, the researchers noted.

The results also showed that vitamin D supplements promoted similar, but less pronounced, anti-inflammatory responses in first-degree relatives of MS patients, suggesting that these supplements may be used as an MS preventive approach.

The study, “The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives,” was published in the journal PLOS ONE.

While the underlying mechanisms of MS remain poorly understood, it is thought that a dysregulation of pro- and anti-inflammatory molecules may contribute to the disease. That is why immunomodulatory and anti-inflammatory treatments are considered promising approaches for MS.

Increasing evidence points to vitamin D as a potentially important immunomodulator in MS. Several studies have shown that MS patients have lower-than-normal levels of vitamin D, and that low levels may raise a person’s risk of developing the disease, or a patient’s risk of relapse and earlier disability.

MS patients with vitamin D deficiency show a more pronounced molecular shift toward a pro-inflammatory state, suggesting that vitamin D may have an immunomodulatory effect that favors the production of anti-inflammatory molecules.

In a previous study, a team of researchers in Iran evaluated the effects of vitamin D supplements in pro- and anti-inflammatory molecules in MS patients, their first-degree relatives, and healthy people.

Based on the results, the researchers proposed a model in which adequate levels of vitamin D promote the production of IL-10, a major anti-inflammatory molecule, and lowers the levels of two pro-inflammatory molecules, IL-17A (also known as IL-17) and IL-6. Notably, these effects were more pronounced in MS patients.

Now, the same team has identified two key drivers of vitamin D’s immunomodulatory effects — IL-27 and TGF-beta 1. While both proteins have the ability to induce pro-and anti-inflammatory responses, evidence suggests they are involved mainly in promoting the latter.

Researchers first analyzed the production of IL-27 and TGF-beta 1 before and after vitamin D supplementation — 50,000 IU orally once a week for two months — in blood cells of 25 MS patients, 25 first-degree relatives, and 25 healthy, unrelated individuals.

Data showed that vitamin D supplements significantly boosted the production of both molecules in all groups, but was more pronounced in MS patients.

The team then measured the blood levels of anti-inflammatory molecules (IL-27, TGF-beta 1, IL-10) and pro-inflammatory molecules (IL-17 and IL-6) before and after vitamin D treatment in all groups of participants.

Before treatment, MS patients had significantly lower levels of anti-inflammatory molecules (IL-27 and IL-10), and higher levels of pro-inflammatory proteins (IL-17A and IL-6) than the other two groups. No significant differences were found in TGF-beta 1 blood levels between the three groups.

Vitamin D administration significantly increased the levels of the anti-inflammatory molecules and decreased the levels of the pro-inflammatory molecules in MS patients, indicating a shift toward an anti-inflammatory state.

Regarding TGF-beta 1 blood levels upon vitamin D treatment, they were increased in MS patients.

Overall, the findings suggested that IL-27 and TGF-beta 1 “are key regulators of IL-10, IL-17A, and IL-6 production,” the researchers wrote, adding that they “could have a major role in the immunomodulatory function and … contribute to the prevention of the [disease-associated] process of MS.”

Similar changes were found for IL-27, IL-10, and IL-6 in MS patients’ relatives. This suggests that first-degree relatives may benefit from vitamin D supplements as a preventive strategy, the researchers noted.

Based on the data, the team proposed a more complete model in which vitamin D boosts the production of IL-27 and TGF-beta 1, both of which directly increase the levels of IL-10 and promote the reduction of IL-17 levels, which then regulates IL-6 production.

Researchers also emphasized that since there is inconsistent data on the roles of IL-27 and TGF- beta 1 in MS, further studies are required to confirm these findings and to clarify the clinical outcomes of these vitamin D-induced molecular changes in MS patients.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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